1. Field of the Invention
Embodiments of the present invention are directed in general to the field of high-resolution, high-sensitivity nuclear and/or electron spin resonance detection. More specifically, the present invention is directed to evanescent wave probe (EWP) techniques used in conjunction with scanning tunneling microscopy (STM) to detect nuclear and/or electron spin resonance.
2. State of the Art
In the discussion of the state of the art that follows, reference is made to certain structures and/or methods. However, the following references should not be construed as an admission that these structures and/or methods constitute prior art. Applicants expressly reserve the right to demonstrate that such structures and/or methods do not qualify as prior art against the present invention.
Spectroscopy and imaging technologies based on magnetic resonance, e.g., electron spin resonance (ESR), also known as electron paramagnetic resonance (EPR), and nuclear magnetic resonance (NMR) have in the past played critical roles in characterizing fundamental properties of molecular structure and materials as well as playing critical roles in medical diagnosis. Dramatic advances in nano-technology, quantum computing, proteomics, combinatorial screening of catalysts and the monitoring of other chemical reactions involving free radicals, and biomedical sciences such as drug screening, have increased the sensitivity requirements for nanoscale spatially resolved magnetic resonance spectroscopy and imaging technologies.
Spin label EPR and NMR spectroscopy is a very powerful tool for determining three dimensional (3-D) protein structures/functionality and protein-ligand interaction in drug-screening. Relative to X-ray structural determination, EPR and NMR do not require protein crystal growth, which requirement is a major disadvantage of the x-ray technique, and thus one may study proteins under physiological conditions using EPR and/or NMR. Electron paramagnetic resonance (EPR) spectroscopy of a site-directed spin label (SDSL) on proteins can reveal protein motion and determine protein structure of any size. Compared to fluorescence spectroscopy techniques, in which fluorescent tags are attached to proteins, spin labels are much smaller and less likely to interfere with the protein's native structure and movement. Spin label-EPR techniques are more sensitive and require less protein than NMR, but current instrumentation is much less sensitive than fluorescence spectroscopy. In addition, commercial instrumentation currently available lags behind NMR by about 20 years in that a time resolved pulse measurement capability is not available (due to some fundamental difficulties in instrumentation development). This has slowed and hampered the adaptation of the new SDSL technology in bio-technology.
A typical magnetic resonance (NMR or ESR) system applies radiation in either the RF or microwave region of the electromagnetic spectrum to a sample already subjected to an external magnetic field, wherein the applied radiation may be either continuous or pulsed, and the radiation having a frequency that is tuned to the specific nuclear or electron spin resonance under consideration. The protons (in the case of NMR) or the electrons (in the case of ESR) absorb the energy and precess coherently at a particular frequency in a particular direction. The resonance frequency v of a spin is proportional to the external magnetic field B, and the energy of absorption hv=gμB, where h is Planck's constant, g is Landé g factor, and μ is either the nuclear magneton μN for the NMR case, or the Bohr magneton μB for the case of ESR.
In a typical nuclear spin resonance experiment, electronic shielding of nuclear spins will induce a very small so-called “chemical shift” to the nuclear spin resonance. It is possible to measure this small shift when the sample has been placed in a highly uniform magnetic field B0, since the nuclear spin resonance line width is extremely narrow. One of the most powerful features and capabilities of conventional NMR is the structural determination that is possible through precise measurement of the chemical shift. Any non-uniformity in the static magnetic field will tend to smear out the small chemical shift and render a NMR instrument useless for structure determination. In this situation, NMR machines have only the capability of structural determination with large volumes of homogenous specimens, and cannot provide significant spatial resolution.
In contrast, magnetic resonance imaging (MRI) does have the capability of imaging with a certain spatial resolution, which is usually in the mm range. This capability is realized through a high magnetic field gradient generated in the specimen such that the spatial resolution is proportional to the degree of the gradient. Three-dimensional MRI imaging is achieved typically by applying a linear magnetic field gradient during the period that the RF pulse is applied. The field gradient determines a sensitive slice in which the resonance condition, a local function of the applied field, is met. This gradient magnetic field is turned on and off very rapidly, altering the main magnetic field on a very local level. When the RF pulse is turned off, the precessing hydrogen protons slowly decay back to their thermal equilibrium states. An induced transient induction signal in a magnetic resonance experiment is detected using a pickup coil, and the signal is sent to a computer system for processing.
In the magnetic resonance imaging technique the presence of a field gradient smears out chemical shifts and the different resonance peaks (similar nuclear spin resonances having different chemical shifts) become one broad peak. The MRI resonance peak is at least 100 times broader than normal NMR peak. Consequently, conventional MRI imaging techniques lacks the capability of spectroscopy and structural determination. Furthermore, chemical shifts in nuclear spin resonance also limit the spatial resolution of MRI, since a 10 ppm typical chemical shift determines the MRI spatial resolution to an order of millimeters.
In the past, magnetic resonance experiments have been conducted in conjunction with scanning tunneling microscopy (STM), the latter being a revolutionary technique that is capable of atomic resolution. In recent years, ESR-STM has been reported to be able to detect the local precessing of spins on the surface of a semiconducting or conducting material, enabled by observing the microwave modulation of the tunneling current induced by precessing spins when an external magnetic field is applied. This phenomenon has been interpreted as a consequence of the spin-orbital coupling at a single atomic site, where the electron populates a mixed state of two electron spin states (Zeeman levels) split by the applied magnetic field. However, current magnetic resonance-STM experiments rely on the production of spin precessing by random thermal fluctuations. Furthermore, the reported data from these experiments has not been widely reproduced and accepted due to limited sensitivity, and difficulties in impedance matching between the RF portions of the experimental configuration (typically 50 ohms) and the high impedance tunneling current circuits.
What is needed is a method of inducing spin precession and excitation between spin states that does not rely on random thermal fluctuations, such that nuclear and/or spin resonance techniques may be carried out with increased resolution and sensitivity.